Protecting groups for RNA synthesis: an increasing need for selective preparative methods.

RNA can be chemically synthesized by automated DNA/RNA synthesizers, using protected ribonucleosides activated as phosphoramidites. The efficiency of the synthesis depends greatly on the protecting groups used, especially the protecting group on the 2'-hydroxyl functionality. The strategies employed to place the protecting groups on the desired functionality are quite inefficient, requiring additional modifications of the substrate, or leading to mixtures of protected compounds. In this tutorial review, the methods available for the selective protection of ribonucleosides are commented on, introducing the reader to the synthetic challenges involved.